In recent years, there have been found out a number of physiologically active proteins, polypeptides, synthetic compounds, compounds extracted from natural sources and so on. Thus, intensive studies have been made to apply these substances to medicines. Also, attempts have been made to develop drug delivery systems (DDSs) in order to improve the selective delivery of a physiologically active substance such as a drug to a target site while reducing its side effect. As these DDSs a method which comprises modifying a polypeptide in, for example, a protein preparation with a hydrophilic polymer such as polyethylene glycol and a method which comprises encapsulating a drug or the like in microparticles such as a polymer micelle are now under study. In these methods, use is made of a polymer into which a biodegradable unit such as a peptide or polylactic acid has been introduced not only for enhancing the drug retention in the blood but also for sustainedly releasing the drug at a target site.
Moreover, biodegradable polymers such as polylactic acid and polyglycolic acid have been widely employed in order to enzymatically or non-enzymatically hydrolyze a drug, which has been sustainedly released into the body, into nontoxic components followed by metabolism and absorption in vivo. More specifically speaking, these polymers, which form crosslinked polymers via gelation of multiple components, are employed in a drug release device, a suture thread/bone-fixing agent, a hemostatic agent, a tissue adhesion inhibitor and so on.
Known examples of these crosslinked polymers are as follows. That is, WO 97/22371 proposes a crosslinkable polymer composition to be used in preventing surgical adhesion, drug delivery and so on which comprises a mixture of a synthetic polypeptide or polyethylene glycol having a plural number of nucleophilic groups such as a primary amino group or a thiol group (—SH) with a hydrophilic or hydrophobic polymer having an electrophilic group such as a succinimidyl group.
Further, WO 00/62827 discloses a composition to be used as a hemostatic/adhesive material or a tissue adhesion inhibitor in vivo during a surgical operation which comprises a compound having a plural number of thiol groups (—SH) as a first component and a compound having a plural number of thiol-reactive groups as a second component, wherein at least one of the first and second components is a polyalkylene oxide and these components react with each other to form a gel. Into this composition, however, no biodegradable group such as polylactic acid is introduced.
Furthermore, U.S. Pat. No. 5,410,016 proposes a polymer compound prepared by introducing an oligo(polyhydroxy acid) such as polylactic acid or polyglycolic acid into a compound having four hydroxyl groups (α-, ω- and two hydroxyl groups on bisphenol A linker) in a bifunctional polyethylene glycol (α-, ω-) and a bifunctional polyethylene glycol attached to bisphenol A bisepoxide and then introducing an acrylic group to a terminus thereof.